This Program consists of five projects. In each project we will study neurons dissociated from the hippocampal formation of rats, making use of cell-culture methods. Our goals, broadly sketched, are: to learn more about the mechanisms of seizure-like activity and associated neuronal pathology in a cell-culture model of seizures; to learn more about factors from the hippocampus that may control the transmitter status of its inputs, and to explore a possible role for such factors in Alzheimer's disease; to learn more about the mechanisms by which steroid hormones regulate activity and damage in hippocampal neurons; to learn more about the voltage-gated and ligand-gated channels through which enters hippocampal neurons and, if the entry is excessive, causes damage; to use monoclonal antibodies to detect, and to begin to isolate, substrate molecules important for neurite outgrowth in the hippocampal formation in order to better understand the limitations on axonal regeneration and repair in the central nervous system. A central concern of this Program is with mechanisms that can lead to abnormal activity, damage or death of hippocampal neurons. In some cases the neuronal damage appears to result from excessive activation of normal cell mechanisms, and we are interested in these normal mechanisms as well. We are also concerned with factors that may help to mitigate, repair or compensate for the damage of these neurons.